GrayBug OIS Presentation

Jeffrey L. Cleland,PhD Interim CEO

N o v e m b e r 1 2 , 2 0 1 5

60CONFIDENTIAL AND PROPRIETARY |

Company Highlights

Ocular Therapeutics Represents a $10B+ Global and Growing Market

GB-102, a Dual Anti-VEGF/Anti-PDGF Therapeutic, Enables Once Every 4 to 6 Month Intravitreal Injections (2-3 vs ≥ 20 injections per year)

• On track for IND in 2016 for wet AMD indication

GrayBug Technology Solves Key Challenges for Sustained Ocular Delivery• Injection with small gauge needle – no surgical procedure• Minimal side-effects, no interference with visual axis• Tunable approach – release rate and duration

Exclusive Rights for Technology• Worldwide rights from Wilmer Eye Institute, Johns Hopkins University• Patent Protection to at least 2030 (additional filings ongoing)

Technology Enables Broad Portfolio of Ocular Products• Age-related macular degeneration (wet & dry), glaucoma, neuroprotection, etc• NCEs for glaucoma and neuroprotection as a novel technologies• Potential for Product Specific Partnerships; Aerie Pharmaceuticals Deal

Experienced and Knowledgeable Team• Ophthalmology & Drug Delivery Experts

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An Experienced LeadershipTeam

Jeffrey Cleland, PhDInterim CEO Board Member

Former CEO, Co-Founder, Versartis>20 Years of Drug Development ExperienceTeam Leader Through Launch of Only FDA Approved Long-Acting hGH Product; Early development of Lucentis

Christy Shaffer,PhDBoard Member Partner, Hatteras Ventures; Former CEO, Inspire

Gerald Cagle,PhDBoard Member Former CSO, Senior VP R&D, Alcon

Justin Hanes, PhD Founder, Chair SAB Board Member

Lewis J. Ort Professor of Ophthalmology & Director of the Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins School of Medicine

Peter Campochiaro,MDFounder, SAB Member

Eccles Professor of Ophthalmology and Neuroscience, Wilmer Eye Institute, Johns Hopkins School of Medicine

Peter McDonnell, MDFounder, SAB Member

William Holland Wilmer Professor and Chair of Ophthalmology, Director of the Wilmer Eye Institute, Johns Hopkins School of Medicine

OPHTHALMOLOGY & INTRAOCULAR THERAPY

LONG ACTING PRODUCTS

VRS-317

ACADEMIC OPHTHALMOLOGY

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GrayBug Technology Advantages

• Tunable release profile (up to 6+ months)

• Injection with small gauge needle (27-29 G)

• Minimizes inflammation

• Forms implant outside visual axis

• Ability to deliver compounds with different properties from small molecules to biologics

• Scalable aseptic manufacturing process (no terminal sterilization required)

In vivo data to date (rabbits):>3 month sustained delivery, no inflammation or toxicity

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Injectable High Capacity Reservoirand Localization of Microparticles

INTRAVITREAL INJECTION WITH SMALL GAUGE NEEDLE

ENCAPSULATED DRUG

Biodegradability Biocompatibility Bioabsorbability

Polymer Modifiedto Reduce

Inflammation

FUNDUS PHOTOS, DAY 7Microparticle Localization

Designed to Aggregate and Remain Outside Visual Axis

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Mea

nA

rea

of

CN

V(m

m2)

Control (PBS)

GB-102(10 ug)

0

0.012

0.008

0.004

0.016

P<0.05

GB-102: Long-Term Suppressionof Neovascularization

Laser-Induced Model of CNV; P.Campochiaro MD, J.Hanes PhD - Wilmer Eye Institute

SUSTAINED EFFICACY: 5 WEEKS(Laser at 4 weeks)

SUSTAINED EFFICACY: 9 WEEKS(Laser at 8 weeks)

P<0.05

Mea

nA

rea

of

CN

V(m

m2)

GB-102 Control (10 ug) (PBS)

0

0.01

0.02

0.03

Control

GB102

Lucentis® lasts only 2 weeks in mouse model

Control

GB102

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Challenges with Current GlaucomaDrugs

• Current approved glaucoma products require daily or BID topical dosing

• Patients are non-compliant with therapy (72% in controlled setting; 50% or less in clinical practice; Quigley et al)

• Lack of compliance leads to neurological complications and loss of vision

– No compounds are approved for neuroprotection & trials may be challenging to prove effects

• Sustained release versions of prostaglandins (PG; e.g. lantanoprost, travoprost) are in development

• Sustained release of carbonic anhydrase inhibitors (CAIs) complicated by solubility in aqueous solutions

• Need drugs with IOP lowering and neuroprotection

Library of compounds being synthesized to address these challenges

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GrayBug Pipeline :GB-102 Lead Product

FORMULATION IN VIVO NON-GLP GLP PROJECTED

INDICATION DEVELOPMENT EFFICACY PK/PD TOXICOLOGY STUDIES IND PHASE 1 PHASE 2

GrayBug’s Focus on GB-102 Enables Potential for:- First and Best in Class, Single Dose Dual Inhibitor with 4-6 Month Dose Interval- Rapid Validation of GrayBug Technology in Humans- Expansion of Patent Portfolio- Ability to Leverage GB-102 Experience to Partner Programs

Wet AMD GB-102 2016 2016 2018

Glaucoma IOP Lowering

Neuroprotection2017

Corneal Graft Rejection

Wet AMD AR13154+ others

Thank You